Search Results (197)

Myeloid-derived growth factor (MYDGF), named in reference to its secretion from myeloid cells in bone marrow, is a novel protein with anti-apoptotic and tissue-repairing properties. MYDGF is found in various human tissues affected by different diseases. To date, however, MYDGF expression has yet to be reported in the nervous system. Herein, we demonstrate for the first time that MYDGF mRNA levels increased in the zebrafish retina 1 h after optic nerve injury (ONI). MYDGF-producing cells were located in the photoreceptors and infiltrating leukocytic cells. We prepared the retina for MYDGF gene knockdown by performing intraocular injections using either MYDGF-specific morpholino or the CRISPR/Cas9 system. Under these MYDGF-knockdown retinal conditions, anti-apoptotic Bcl-2 mRNA was suppressed; in comparison, apoptotic caspase-3 and inflammatory TNFα mRNA were significantly upregulated in the zebrafish retina after ONI compared to the control. Furthermore, heat shock factor 1 (HSF1) was evidently suppressed under these conditions, leading to a significant number of apoptotic neurons. These findings indicate that MYDGF is a key molecule in the stimulation of neuronal regeneration in the central nervous system. Full article

Background/Objectives: Moso bamboo (Phyllostachys edulis), the most widely distributed bamboo species in China, is valued for both its shoots and timber. This species often faces challenges from high-temperature stress. To cope with this stress, Moso bamboo has evolved various adaptive mechanisms at the physiological and molecular levels. Although numerous studies have revealed that a large number of transcription factors (TFs) and genes play important roles in the regulatory network of plant heat stress responses, the regulatory network involved in heat responses remains incompletely understood. Methods: In this study, Moso bamboo was placed in a high-temperature environment of 42 °C for 1 h and 24 h, and transcriptome sequencing was carried out to accurately identify key molecules affected by high temperature and their related biological pathways. Results: Through a differential expression analysis, we successfully identified a series of key candidate genes and transcription factors involved in heat stress responses, including members of the ethylene response factor, HSF, WRKY, MYB, and bHLH families. Notably, in addition to traditional heat shock proteins/factors, multiple genes related to lipid metabolism, antioxidant enzymes, dehydration responses, and hormone signal transduction were found to play significant roles in heat stress responses. To further verify the changes in the expression of these genes, we used qRT-PCR technology for detection, and the results strongly supported their key roles in cellular physiological processes and heat stress responses. Conclusions: This study not only deepens our understanding of plant strategies for coping with and defending against extreme abiotic stresses but also provides valuable insights for future research on heat tolerance in Moso bamboo and other plants. Full article

Heat shock transcription factor (Hsf) plays a pivotal role in regulating plant growth, development, and stress responses. Hsf activates or represses target gene transcription by binding to the heat shock element (HSE) of downstream genes. However, the specific interaction sites between Hsf and the HSE in the promoter remain unclear. In this study, the critical amino acid residues of ZmHsf17 and the paralogous ZmHsf05 involved in DNA binding were identified using molecular docking models, site-directed mutagenesis, and the electrophoretic mobility shift assay (EMSA). The results reveal that both ZmHsf17 and ZmHsf05 bind to the HSE of the ZmPAH1 promoter via a conserved arginine residue located in the α3 helix of their DNA-binding domains. Sequence substitution experiments among distinct HSEs demonstrated that flanking sequences upstream and downstream of the HSE core synergistically contribute to the specificity of DNA-binding domain recognition. Comparative evolutionary analysis of DNA-binding domain sequences from 25 phylogenetically diverse species reveals that the α3 helix constitutes the most conserved structural element. This study elucidates the key interaction sites between maize HsfA2 and its target genes, providing theoretical insights into the binding specificity to the HSEs of the plant’s Hsf family and the functional divergence. Additionally, these findings offer new targets for the precise engineering of Hsf proteins and synthetic HSEs. Full article

Thermal manipulation (TM) during embryogenesis is a promising non-pharmacological strategy to enhance physiological resilience in broiler chickens. This study evaluated the impact of thermal conditioning of fertile eggs on growth performance, inflammatory responses, and molecular stress markers following a post-hatch lipopolysaccharide (LPS) challenge. Fertilized eggs (average weight 62 ± 3 g) were obtained from 35-week-old Indian River broiler breeder hens. A total of 720 eggs were randomly assigned to either the control group (n = 360) or the TM group (n = 360), with each group consisting of two replicates of 180 eggs. Control eggs were maintained under standard incubation conditions (37.8 °C, 56% RH), while TM eggs were subjected to elevated temperature (38.8 °C, 65% RH) for 18 h daily from embryonic day 10 to 18. On post-hatch day 15, control and TM groups were administered either saline or LPS via intraperitoneal (IP) injection. Body weight and temperature, internal organ weights, and splenic mRNA expression levels of inflammatory cytokines, toll-like receptors, transcription factors, and heat shock proteins were assessed. TM did not alter hatchability (p = 0.633), but significantly shortened hatch time (p < 0.05) and improved feed efficiency (p < 0.05). While LPS induced marked inflammatory responses in all birds, those subjected to TM exhibited attenuated proinflammatory cytokine expression, enhanced anti-inflammatory signaling, and differential regulation of stress-associated genes, including nuclear factor kappa B (NF-κB), heat shock protein 70 (HSP70), and heat shock factors (HSFs). These findings suggest that TM during incubation promotes a more regulated immune response and improved stress adaptation post-hatch. This approach offers a potential antibiotic-free intervention to enhance broiler health, performance, and resilience under immunological stress. Full article

Begonia semperflorens (B. semperflorens) is a popular ornamental plant widely used in landscapes such as plazas and flower beds, and it is also commonly grown as a potted plant indoors. It is known for its adaptability to high temperatures, drought, and shade. Under heat-tolerant conditions, heat shock transcription factors (HSFs) are key transcriptional regulatory proteins that play crucial roles in cellular processes. Despite extensive studies on the HSF family in various species, there has been no specific analysis targeting B. semperflorens. In this study, we identified 37 members of the BsHSF gene family in B. semperflorens based on its genome scaffold, which are unevenly distributed across the genome. Phylogenetic analysis reveals that these 37 members can be divided into three subfamilies. Analysis of their physicochemical properties shows significant diversity among these proteins. Except for the BsHSFB7 protein located in the cytoplasm, all other BsHSF proteins were found to be nuclear-localized. A comparison of the amino acid sequences indicates that all BsHSF proteins contain a conserved DNA-binding domain structure. Analysis of the promoter cis-acting elements also suggests that BsHSFs may be associated with heat stress and plant secondary metabolism. We further investigated the duplication events of BsHSF genes and their collinearity with genes from other Begonia species. Finally, through real-time quantitative PCR, we examined the expression patterns of the 37 BsHSFs in different plant tissues (roots, stems, leaves, and flowers) and their expression levels under heat stress treatment. The results show that, except for BsHSF29, all BsHSFs were expressed in various tissues, with varying expression levels across tissues. Except for BsHSF33 and BsHSF34, the expression levels of almost all BsHSF genes increased in response to heat treatment. In summary, these findings provide a better understanding of the role and regulatory mechanisms of HSFs in the heat stress response of B. semperflorens and lay the foundation for further exploration of the biological functions of BsHSFs in the stress responses of B. semperflorens. Full article

Chinese tongue sole (Cynoglossus semilaevis) is an important marine fish in China. It has sexual dimorphism. The weight and growth rate of female fish are much greater than those of male fish. However, high temperatures can induce sex reversal in genetic female fish (ZW) to phenotypic male fish; thus, identifying the genetic elements involved in temperature perception will provide the molecular basis for sex control. The heat shock transcription factor (hsf) is known as an important component of temperature sensing and mediates the heat shock response in fish such as Danio rerio; however, its function in C. semilaevis is unclear. In this study, five hsf genes (hsf1, hsf2, hsf4, hsf5a, and hsf5b) were identified in tongue sole and found to be expressed in the gonads at different developmental stages, peaking from 7M to 1Y. Gonadal in situ hybridization revealed that hsf gene signals were mainly localized in germ cells, e.g., sperm in the testis and all-stage oocytes in the ovary. Upon high-temperature stimulation, the expression of the hsf gene in the gonads increased gradually with increasing stimulation time, but different hsf genes presented different response patterns. After the RNA interference of hsf in the testis and ovarian cell lines, a series of sex-related genes, such as foxl2 and dmrt1, significantly changed. In vivo RNA interference had an effect on the female gonads and mainly affected neurl3 expression. On the basis of these data, we speculate that hsf responds to temperature stimulation and plays an important role in sex differentiation. This study helps elucidate the relationship between temperature sensing and sex differentiation in C. semilaevis. Full article

Panax ginseng plants are susceptible to high temperatures and intense sunlight, necessitating cultivation under artificially shaded structures. Identifying the genes associated with heat resistance is critical for advancing molecular breeding strategies to develop heat-tolerant ginseng varieties. Heat-shock transcription factors (HSFs) are widely recognized as key regulators of plant responses to abiotic stresses, primarily by controlling heat-shock proteins (HSPs). To identify HSF genes in P. ginseng, transcriptome analysis was conducted on ginseng plants subjected to heat-shock treatment (1 h at 40 °C). Among the 26 HSF unigenes annotated from the ginseng transcriptome, a unigene related to the HSFA2 family exhibited the highest transcriptional activity following heat-shock treatment. The expression of PgHSFA2, a gene identified from this unigene, was analyzed under temperature and salt-stress conditions in ginseng plants using qPCR. The results showed that PgHSFA2 was highly responsive to various abiotic stresses, including heat, cold, salt, and intense sunlight. To assess the functional role of PgHSFA2, transgenic tobacco plants overexpressing this gene were analyzed. The overexpression of PgHSFA2 led to an elevated expression of heat-shock proteins (HSPs) in tobacco, resulting in enhanced resistance to high temperature and salt stress. Transgenic tobacco plants exhibited significantly less reduction in chlorophyll fluorescence compared to nontransgenic controls when exposed to salt stress (200 and 400 mM NaCl) and high-temperature stress (42 °C), indicating improved stress tolerance. In conclusion, PgHSFA2 is a crucial HSF that regulates the transcriptional control of HSPs in ginseng plants. The constitutive expression of PgHSFA2 in transgenic ginseng could potentially confer improved tolerance to high temperatures, making it a valuable target for molecular breeding. Full article

Background/Objectives: Prenatal hypoxia (PH) is a leading cause of nervous system disorders in early childhood and subsequently leads to a decline in the cognitive and mnemonic functions of the central nervous system (such as memory impairment, reduced learning ability, and information processing). It also increases anxiety and the risk of brain disorders in adulthood. Compensatory–adaptive mechanisms of the mother–placenta–fetus system, which enhance the fetus’s CNS resilience, are known, including the activation of endogenous neuroprotection in response to hypoxic brain injury through the pharmacological modulation of HSP₇₀. Methods: To evaluate the effect of HSP₇₀ modulators—Cerebrocurin, Angiolin, Tamoxifen, Glutaredoxin, Thiotriazoline, and HSF-1 (heat shock factor 1 protein), as well as Mildronate and Mexidol—on the motor skills, exploratory behaviors, psycho-emotional activities, learning, and memories of offspring after PH. Experimental PH was induced by daily intraperitoneal injections of sodium nitrite solution into pregnant female rats from the 16th to the 21st day of pregnancy at a dose of 50 mg/kg. The newborns received intraperitoneal injections of Angiolin (50 mg/kg), Thiotriazoline (50 mg/kg), Mexidol (100 mg/kg), Cerebrocurin (150 µL/kg), L-arginine (200 mg/kg), Glutaredoxin (200 µg/kg), HSF-1 (50 mg/kg), or Mildronate (50 mg/kg) for 30 days. At 1 month, the rats were tested in the open field test, and at 2 months, they were trained and tested for working and spatial memory in the radial maze. Results: Modeling PH led to persistent impairments in exploratory activity, psycho-emotional behavior, and a decrease in the cognitive–mnestic functions of the CNS. It was found that Angiolin and Cerebrocurin had the most pronounced effects on the indicators of exploratory activity and psycho-emotional status in 1-month-old animals after PH. They also exhibited the most significant cognitive-enhancing and memory-supporting effects during the training and evaluation of skill retention in the maze in 2-month-old offspring after PH. Conclusions: for the first time, we obtained experimental data on the effects of HSP₇₀ modulators on exploratory activity, psycho-emotional behavior, and cognitive–mnestic functions of the central nervous system in offspring following intrauterine hypoxia. Based on the results of this study, we identified the pharmacological agents Angiolin and Cerebrocurin as promising neuroprotective agents after perinatal hypoxia. Full article

Heat stress is one of the major factors affecting crop growth and yield. However, the molecular mechanisms underlying rice heat stress tolerance remain largely unclear. In this study, we identified and characterized the rice high temperature sensitive 2 (hts2) mutant, which is highly susceptible to heat stress. Map-based cloning revealed that the HTS2 encodes a cytochrome P450 protein (CYP71P1) involved in serotonin biosynthesis. HTS2 is ubiquitously expressed across plant tissues and shows strong upregulation in response to heat stress. The HTS2 mutation significantly impairs basal serotonin synthesis in rice, and the heat-sensitive phenotype of the hts2 mutant is completely rescued by exogenous serotonin supplementation. Compared to the wild type, the hts2 mutant exhibits reduced antioxidant capacity, leading to excessive reactive oxygen species (ROS) accumulation and severe oxidative damage, ultimately reducing heat stress tolerance. Furthermore, disruption of HTS2 significantly affects the rice heat shock response, with the heat-induced expression of HsfA2s and their downstream target genes, such as HSP18.0 (heat shock protein 18.0) and OsAPX2 (ascorbate peroxidase 2), markedly depressed in hts2 mutant. Our results suggest a pivotal role of HTS2 in modulating serotonin metabolism and maintaining ROS homeostasis during heat stress, offering new perspectives on the mechanisms underlying heat tolerance and potential strategies to enhance rice resilience to heat stress. Full article

Heat shock transcription factor (Hsf) plays a crucial role in the signal transduction pathways of plants in response to drought stress. However, studies exploring the specific functions and mechanisms of action of the Hsf family in tea plants (Camellia sinensis L.) remain limited. In this study, we identified 31 members of the CsHsf family from the C. sinensis genome. CsHsf10 was determined to be a potential drought-resistant candidate gene by screening 10 highly expressed genes in mature leaves and confirming results through RT-qPCR. Correlation analysis indicates that CsHsf10 may enhance the drought resistance of tea plants by participating in the tea polyphenol synthesis pathway and regulating the expression of antioxidant enzyme genes. Furthermore, overexpression experiments in Arabidopsis and antisense oligonucleotide experiments in tea plants corroborated that CsHsf10 exerts a significant positive regulatory effect on drought resistance in tea plants. Yeast one-hybrid assays and dual luciferase reporter gene experiments demonstrated that CsHsf10 can directly target CsPOD17, significantly promoting its transcriptional expression. Additionally, we found that the expression of CsHsf10 contributes to the increased accumulation of catechin components in tea plants under drought stress. These findings suggest that, during the response of tea plants to drought stress, CsHsf10 not only enhances antioxidant capacity by regulating the activity of antioxidant enzymes but also optimizes the physiological state of tea plants by influencing the accumulation of secondary metabolites, thereby significantly improving their drought resistance. Full article

The tea plant (Camellia sinensis) is an economically important crop that plays an important role not only in the beverage industry but also in the pharmaceutical industry. The environment has a great influence on the quality of the tea plant. Heat shock factors (Hsfs) are transcriptional regulators that control the plant response to adversity. However, only a limited number of studies have reported the Hsf gene in Camellia sinensis, and most of these reports involve high-temperature, drought, and salt stress. Research on light, dark, and cold stress is limited. In this study, 22 CsHsf genes were obtained by whole genome sequencing and found to be located on 11 chromosomes. In addition, the gene structure, protein motif, and phylogeny were studied. We classified the genes into three major subfamilies: CsHsfA, CsHsfB, and CsHsfC. Interestingly, we found that there was more alignment between CsHsf and Hsf genes in dicotyledons, including Arabidopsis thaliana and Solanum lycopersicum, than in the monocotyledon Oryza sativa. The expression of many CsHsf genes was affected by low-temperature, light, and dark abiotic stresses. Notably, CsHsf15 and CsHsf16 showed high induction rates under both light and cold stress, and both genes carried cis-acting elements associated with light and low-temperature responses. These results lay a solid groundwork for further investigations into the involvement of CsHsf genes in the response of Camellia sinensis to abiotic stresses. Full article

Recently, immune checkpoint inhibitors (ICIs) and cabozantinib, a tyrosine kinase inhibitor (TKI), have been used to treat renal cell carcinoma (RCC); the combination of these agents has become a standard treatment for RCC. TKIs generally target vascular endothelial growth factor. However, cabozantinib is characterized by its targeting of MET. Therefore, cabozantinib can be used as a late-line therapy for TKI-resistant RCC. According to data from The Cancer Genome Atlas (TCGA), heat shock transcription factor 4 (HSF4) expression is higher in RCC tissues than in normal renal tissues. HSF4 binds to the MET promoter in colorectal carcinoma to enhance MET expression and promote tumor progression. However, the functional role of HSF4 in RCC is unclear. We performed loss-of-function assays of HSF4, and our results showed that HSF4 knockdown in RCC cells significantly decreased cell functions. Moreover, MET expression was decreased in HSF4-knockdown cells but elevated in sunitinib-resistant RCC cells. The combination of cabozantinib and HSF4 knockdown reduced cell proliferation in sunitinib-resistant cells more than each monotherapy alone. Furthermore, HSF4 knockdown combined with an ICI showed synergistic suppression of tumor growth in vivo. Overall, our strategy involving HSF4 knockdown may enhance the efficacy of existing therapies, such as cabozantinib and ICIs. Full article

Heat shock factors (HSFs) are transcription factors that regulate responses to environmental changes and play roles in physiological mechanisms like spermatogenesis. This study analyzed the HSF gene family and their expression profiles in the European eel under different environmental conditions and during testis maturation. Six HSF genes were identified in the studied vertebrates, in which the eel presents two HSF1 paralogs (HSF1a and HSF1b), likely resulting from the teleost whole-genome duplication event, while only one paralog is present for the other HSF (HSF2, HSF4, and HSF5). All five HSF genes were highly expressed in the testis, but some were also detected in the brain, intestine, and gills. Our findings showed that HSF1 changed their expression in response to different temperature and salinity conditions, suggesting that these may support males in perceiving the temperature and salinity changes possibly found during reproductive migration. During hCGrec-induced spermatogenesis, HSF genes presented a decreasing expression profile throughout testis maturation (with significant differences in HSF1a and HSF4), except HSF5, which showed the highest levels after 4 weeks of hormonal treatment. Our study indicates that HSF genes are potentially implicated in the response to environmental changes perception and during gonadal maturation. Full article

Background/Objective: Ovarian cancer (OC) is one of the most lethal gynecological cancers, having a worldwide mortality rate of 66% in 2020. The overall 5-year relative survival rate is only 21% for distant stages, due to the lack of early diagnosis. Epithelial OC, the most common high-grade serous carcinoma, carries p53 mutations in most cases. However, we found that the immediate early response 5 gene (IER5), a p53 target gene, is overexpressed in ovarian cancer cells. The molecular mechanism underlying the role of IER5 in OC has not been well studied. We previously reported that IER5 promotes the dephosphorylation and activation of heat shock factor-1 (HSF1), the master regulator of proteostasis, which induces heat shock protein (HSP) expression. Methods/Results: Here we show that Ier5 mRNA expression is higher in ovarian cancer cells (MOV, ID8G, and HM-1) compared to normal ovarian cells. We also show that OC cells floating in the ascites have higher Ier5 expression than the parental strain. Knockdown of Ier5 suppressed HSP upregulation and proliferation of OC, while overexpression of IER5 promoted HSP upregulation. Knockdown of Hsf1 showed results similar to Ier5 knockdown. Conclusions: These results indicate that the IER5-HSF1 pathway contributes to the proliferation and peritoneal dissemination of OC cells. We also found that higher expression of IER5 family genes is related to poorer prognosis of OC patients, suggesting the potential of the IER5 gene family as diagnostic markers for OC, as well as potential therapeutic targets. Full article

Heat stress is one of the most important environmental problems in agriculture, which severely restricts the growth and yield of plants. In plants, microRNA398 (miR398) negatively regulates the activity of superoxide dismutase (SOD) by modulating the expression of its coding genes (CSDs) post-transcriptionally, thereby regulating reactive oxygen species (ROS) homeostasis and stress resistance. In this study, the role of miR398 in heat stress tolerance in tomato was investigated. Under heat stress, the expression of miR398 was upregulated in tomato, while the expression of its target genes (CSD1 and CSD2) and SOD activity was downregulated. Furthermore, by comparing the heat stress response in wild type (WT) and a transgenic line overexpressing MIR398 (miR398-OE), the results showed that overexpression of miR398 promoted tomato growth and the expression of genes encoding heat shock factor (HSF, transcription factor) and heat shock protein (HSP) under heat stress. Meanwhile, downregulated activity of antioxidant enzymes, including SOD, catalase (CAT), peroxidase (POD), and ascorbate peroxidase (APX), and enhanced ROS accumulation was observed in miR398-OE compared with that in WT under heat stress. Further study using dimethylthiourea (DMTU, a ROS scavenger) indicated that the enhanced plant growth and expression of HSFs/HSPs was based on the promoted accumulation of ROS in miR398-OE. Overall, the results of this study revealed that the upregulated expression of miR398 in response to heat stress would modulate the antioxidant system and enhance ROS accumulation, thereby enhancing the expression of HSFs and HSPs and heat stress tolerance in tomato. Full article